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1.
An. sist. sanit. Navar ; 29(3): 357-366, sept.-dic. 2006. ilus, tab
Artigo em Es | IBECS | ID: ibc-052253

RESUMO

Fundamento. Analizar, en relación a la confidencialidad, los conocimientos, comportamientos y opiniones del personal médico y de enfermería asistente a los 13 seminarios impartidos sobre este tema en el Hospital Virgen del Camino de Pamplona en el año 2002. Material y métodos. Administración, antes del inicio de cada seminario, de una encuesta de 11 preguntas cerradas para su cumplimentación anónima. Resultados. Un 93,0% de los 244 asistentes respondieron la encuesta (128 médicos y 99 enfermeras). El 92,1% de los profesionales entiende qué es la intimidad, pero un 58,1% no conoce ninguna de las leyes que la regulan. El 87,5% de los facultativos sabe cuándo es legítimo acceder a los datos de un paciente, pero reconocen comportamientos contrarios en un porcentaje que va aumentando con la edad, desde un 12,5% en el grupo de menos de 31 años hasta el 51,9% en los mayores de 50 años. Entre el personal de enfermería se recogen prácticas más correctas aun cuando muestran un conocimiento teórico peor sobre estas cuestiones. Un 49,7% de los profesionales ingresaría en otro centro si quisiera que su diagnóstico no se divulgara entre sus compañeros y el 92,2% considera el comentario informal de pasillo la vía más frecuente de ruptura de la confidencialidad en el hospital. Conclusión. Parece oportuno recordar en nuestro hospital la responsabilidad ética y legal en relación a la confidencialidad y propiciar la reflexión de los profesionales sobre estas cuestiones con el fin de mejorar esta dimensión clave de la atención sanitaria


Background. To analyse the knowledge, conduct and opinions concerning confidentiality of the medical and nursing personnel who attended the 13 seminars given on this subject at the Virgen del Camino Hospital in Pamplona in the year 2002. Methods. Distribution before the start of each seminar of a survey of 11 closed questions to be completed anonymously. Results. Ninety-three percent (93.0%) of the 244 professionals attending the seminars responded to the survey (128 doctors and 99 nurses). Ninety-two point one percent (92.1%) of the professionals understand what privacy is, but 58.1% do not know any of the laws that regulate it. Eighty-seven point five percent (87.5%) know when it is legitimate to access the data on a patient, but contrary conduct is recognise in a percentage that increases with age, from 12.5% in the group under 31 years old to 51.9% in those over 50 years of age. More correct practices were recolected amongst nursing personnel even when they show less theoretical knowledge about these questions. Fortynine point seven percent (49.7%) of the professionals would join another centre if they wanted their diagnosis not to be divulged amongst their colleagues, and 92.2% consider informal comments made in the corridors to be the most frequent way of breaking confidentiality in the hospital. Conclusion. It seems timely to call attention to ethical and legal responsibility in our hospital and to encourage reflection amongst professional about this questions of confidentiality in order to improve this key dimension of health care


Assuntos
Humanos , Conhecimentos, Atitudes e Prática em Saúde , Confidencialidade/tendências , Corpo Clínico Hospitalar/ética , Pesquisas sobre Atenção à Saúde/estatística & dados numéricos , Pessoal de Saúde/estatística & dados numéricos
2.
An. sist. sanit. Navar ; 29(supl.3): 49-59, sept.-dic. 2006. tab
Artigo em Es | IBECS | ID: ibc-052276

RESUMO

El secreto siempre ha formado parte de la atención al enfermo. Ya en los albores de la medicina occidental, no decir a otros lo que el médico conociera de su paciente era considerado una exigencia del buen hacer. El cambio sustancial acaecido en las últimas décadas es la transformación del secreto en un derecho ciudadano. El reconocimiento a la autonomía personal del paciente sustenta su derecho a consentir o rechazar las propuestas de los profesionales de la salud y también a decidir quién puede acceder a sus datos personales y qué límites impone al manejo de su cuerpo. Sin embargo, la intimidad de los pacientes sigue siendo vulnerada con frecuencia quizás porque vivimos en una sociedad que trivializa estas cuestiones y el ámbito sanitario no es impermeable a esta manera de pensar. Las nuevas tecnologías de la información han añadido, además, un nuevo peligro facilitando enormemente el acceso a los datos personales. En este artículo se revisan los aspectos éticos y legales sobre este tema, los resultados de una investigación llevada a cabo sobre el modo en que los profesionales de ocho hospitales españoles tratan la confidencialidad y se esbozan algunas recomendaciones en un intento de promover la reflexión de los profesionales que interactúan en un escenario donde el paciente se ve obligado a desnudarse en cuerpo y alma


Secrecy has always been a part of patient care. Already at the dawn of western medicine, not telling others what the doctor might know about his patient was considered a requirement of good practice. A substantial change that has occurred in recent decades is the transformation of secrecy into a citizen’s right. Recognition of the personal autonomy of the patient forms the basis of his right to consent to, or reject, the proposals of the health professionals, and also to decide who can have access to his personal data and what limits he imposes on the handling of his body. Nonetheless, the intimacy of patients frequently continues to be violated, perhaps because we live in a society that trivialises these questions, and the health milieu is not immune to this way of thinking. Besides, the new information technologies have added a new danger by enormously facilitating access to personal data. This article reviews the ethical and legal aspects of this issue, the results of research carried out on the way the professionals of eight Spanish hospitals deal with confidentiality, and some recommendations are outlined in an attempt to encourage reflection by the professionals who interact in a scenario where the patient is obliged to lay himself bare in body and soul


Assuntos
Humanos , Confidencialidade/ética , Acesso à Informação/ética , Notificação de Doenças/legislação & jurisprudência , Direitos do Paciente/legislação & jurisprudência , Relações Médico-Paciente/ética , Prontuários Médicos/legislação & jurisprudência
3.
Apoptosis ; 11(2): 209-19, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16502259

RESUMO

Synthetic peptides with sequences present in extracellular matrix protein fibronectin have been described to stimulate human monocytes. We describe now that one of these peptides, FN6, induces apoptotic effects on monocytes and we investigate the molecular mechanisms involved in the regulation of this response. Incubation of monocytes with FN6 induces the activation of the small GTPase Rac. In turn, Rac mediates the increase of both JNK and p38 activities in a sustained fashion, as well as the phosphorylation levels of their respective substrates c-Jun and ATF-2. FN6 also stimulates caspases -9 and -3 and the delayed proteolysis of its substrates PARP and D4-GDI. In addition, initiator caspases-1 and -5 were activated by FN6 treatment of monocytes but, in contrast to that observed for caspases-9 and -3, this effect was not dependent on JNK or p38 activities. These kinases also mediated the increase of Bax levels, but only in some conditions Bcl-2 depletion caused by the peptide. Moreover, whereas initially only caspase-1 is involved in caspase-3 activation, later on caspase-9 seems also to participate. Therefore, we demonstrate that FN6 stimulation allows multiple, JNK and p38-dependent and -independent interacting signals to regulate the apoptotic response in human monocytes.


Assuntos
Apoptose/efeitos dos fármacos , Fibronectinas/química , Monócitos/efeitos dos fármacos , Peptídeos/farmacologia , Proteínas Reguladoras de Apoptose/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Células Cultivadas , Fragmentação do DNA/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Inibidores de Dissociação do Nucleotídeo Guanina/metabolismo , Humanos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Monócitos/citologia , Fosforilação/efeitos dos fármacos , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Proteínas rac de Ligação ao GTP/metabolismo , Inibidor beta de Dissociação do Nucleotídeo Guanina rho , Inibidores da Dissociação do Nucleotídeo Guanina rho-Específico
4.
An Sist Sanit Navar ; 29(3): 357-66, 2006.
Artigo em Espanhol | MEDLINE | ID: mdl-17224939

RESUMO

BACKGROUND: To analyse the knowledge, conduct and opinions concerning confidentiality of the medical and nursing personnel who attended the 13 seminars given on this subject at the Virgen del Camino Hospital in Pamplona in the year 2002. METHODS: Distribution before the start of each seminar of a survey of 11 closed questions to be completed anonymously. RESULTS: Ninety-three percent (93.0%) of the 244 professionals attending the seminars responded to the survey (128 doctors and 99 nurses). Ninety-two point one percent (92.1%) of the professionals understand what privacy is, but 58.1% do not know any of the laws that regulate it. Eighty-seven point five percent (87.5%) know when it is legitimate to access the data on a patient, but contrary conduct is recognise in a percentage that increases with age, from 12.5% in the group under 31 years old to 51.9% in those over 50 years of age. More correct practices were recollected amongst nursing personnel even when they show less theoretical knowledge about these questions. Forty-nine point seven percent (49.7%) of the professionals would join another centre if they wanted their diagnosis not to be divulged amongst their colleagues, and 92.2% consider informal comments made in the corridors to be the most frequent way of breaking confidentiality in the hospital. CONCLUSION: It seems timely to call attention to ethical and legal responsibility in our hospital and to encourage reflection amongst professional about this questions of confidentiality in order to improve this key dimension of health care.


Assuntos
Atitude do Pessoal de Saúde , Confidencialidade , Ética Profissional , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde , Hospitais , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
5.
An Sist Sanit Navar ; 29 Suppl 3: 49-59, 2006.
Artigo em Espanhol | MEDLINE | ID: mdl-17308539

RESUMO

Secrecy has always been a part of patient care. Already at the dawn of western medicine, not telling others what the doctor might know about his patient was considered a requirement of good practice. A substantial change that has occurred in recent decades is the transformation of secrecy into a citizen's right. Recognition of the personal autonomy of the patient forms the basis of his right to consent to, or reject, the proposals of the health professionals, and also to decide who can have access to his personal data and what limits he imposes on the handling of his body. Nonetheless, the intimacy of patients frequently continues to be violated, perhaps because we live in a society that trivialises these questions, and the health milieu is not immune to this way of thinking. Besides, the new information technologies have added a new danger by enormously facilitating access to personal data. This article reviews the ethical and legal aspects of this issue, the results of research carried out on the way the professionals of eight Spanish hospitals deal with confidentiality, and some recommendations are outlined in an attempt to encourage reflection by the professionals who interact in a scenario where the patient is obliged to lay himself bare in body and soul.


Assuntos
Confidencialidade , Assistência ao Paciente/ética , Privacidade , Humanos
7.
An Sist Sanit Navar ; 27(2): 233-9, 2004.
Artigo em Espanhol | MEDLINE | ID: mdl-15381955

RESUMO

BACKGROUND: To assess the utilization of an electronic medical record (EMR), the degree of satisfaction with this tool, as well as to detect problems in its utilization, in a tertiary hospital in Spain. METHODS: A survey was sent by mail to all physicians in the Virgen del Camino Hospital in Pamplona, Spain. RESULTS: Out of 445 staff physicians, 174 answered the survey (39%). Seventy-nine percent considered that the EMR is better than the traditional, paper-based medical record. Sixty-one percent used the EMR for consultation and to introduce clinical data in a regular way. Fifty-five percent agreed that the EMR has advantages for the patient. The main problems detected are a loss in confidentiality, lack of time, insufficient number of computers, and inadequate training. Ninety percent answered that EMR implementation should be continued and only 6% are dissatisfied with the computer application. CONCLUSIONS: There is a high degree of utilization of the EMR in the Virgen del Camino Hospital. Measures should be implemented to resolve the problems detected in this survey.


Assuntos
Sistemas Computadorizados de Registros Médicos/estatística & dados numéricos , Sistemas Computadorizados de Registros Médicos/normas , Comportamento do Consumidor , Hospitais , Inquéritos e Questionários
8.
FEBS Lett ; 566(1-3): 6-10, 2004 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-15147859

RESUMO

Pemphigus vulgaris (PV) is an autoimmune disease characterized by binding of IgG autoantibodies to epidermal keratinocyte desmosomes. IgG autoantibodies obtained from a patient with mucocutaneous PV reacted with plakoglobin (Plkg) in addition to desmoglein-3 (Dsg3) and Dsg1. Immunofluorescence analysis confirmed that IgG autoantibodies, unlike antibodies from a healthy volunteer, caused disruption of cell-cell contacts in HaCaT keratinocytes. Moreover, apoptosis was enhanced in cells treated with autoantibodies compared to those treated with normal antibodies. The apoptotic process induced by IgG autoantibodies was characterized by caspase-3 activation, Bcl-2 depletion and Bax expression. The present report demonstrates that PV IgG autoantibodies promote apoptosis in HaCaT keratinocytes.


Assuntos
Apoptose/imunologia , Autoanticorpos/farmacologia , Queratinócitos/citologia , Queratinócitos/imunologia , Pênfigo/imunologia , Autoanticorpos/imunologia , Caspase 3 , Caspases/metabolismo , Linhagem Celular Transformada , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Proteínas do Citoesqueleto/metabolismo , Fragmentação do DNA , Relação Dose-Resposta Imunológica , Imunoglobulina G/metabolismo , Queratinócitos/metabolismo , Queratinócitos/ultraestrutura , Microscopia de Fluorescência , Testes de Precipitina , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fatores de Tempo , Proteína X Associada a bcl-2
9.
An. sist. sanit. Navar ; 27(2): 233-239, mayo 2004. tab
Artigo em Es | IBECS | ID: ibc-34528

RESUMO

Fundamento. Evaluar en un hospital terciario, el grado de utilización de una historia clínica informatizada (HCI), las opiniones de los profesionales sobre sus ventajas e inconvenientes y su nivel de satisfacción con la misma. Material y métodos. Encuesta enviada por correo a todos los médicos del Hospital Virgen del Camino en Pamplona. Resultados. De los 445 médicos del centro, contestaron la encuesta 174 (39 por ciento). De éstos, el 79 por ciento consideran que la HCI es mejor que la historia clínica tradicional, el 61 por ciento la utilizan para consultar e introducir datos de manera habitual y el 55 por ciento están muy de acuerdo con que la HCI ofrece ventajas para el paciente. Los principales problemas detectados son la posible pérdida de confidencialidad, y la falta de tiempo, de dotación informática y de mayor formación, para el manejo del programa. El 90 por ciento de los encuestados opina que se debe continuar con su implantación y sólo el 6 por ciento dice estar poco satisfecho con la aplicación. Conclusión. Existe una extendida utilización de la HCI entre los médicos del Hospital Virgen del Camino y su opinión sobre el programa puede considerarse globalmente favorable. Se deben desarrollar medidas para subsanar los problemas detectados mediante este estudio (AU)


Assuntos
Adulto , Feminino , Masculino , Pessoa de Meia-Idade , Humanos , Anamnese Homeopática , Coleta de Dados/métodos , Coleta de Dados , Atenção Terciária à Saúde , Processamento Eletrônico de Dados/organização & administração , Processamento Eletrônico de Dados , Automação/métodos , Automação/normas , Confidencialidade , Automação/classificação , Automação/economia , Automação/instrumentação , Educação/métodos , Educação/organização & administração
10.
FEBS Lett ; 528(1-3): 133-8, 2002 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-12297293

RESUMO

The role of members of the mitogen-activated protein kinase (MAPK) family on tumor necrosis factor alpha (TNF-alpha)-mediated down-regulation of col1a1 gene was studied. TNF-alpha increased extracellular-regulated kinase and Jun-N-terminal kinase phosphorylation, but these effects were not related to its inhibitory effect on alpha1(I) procollagen (col1a1) mRNA levels. Phosphorylation of p38 MAPK was decreased in response to TNF-alpha, and the specific p38 MAPK inhibitor SB203580 mimicked the effect of TNF-alpha on col1a1 mRNA levels. Transforming growth factor beta (TGF-beta) increased p38 MAPK phosphorylation and SB203580 prevented the induction of col1a1 mRNA levels by TGF-beta. These results suggest that p38 MAPK plays an important role in regulating the expression of col1a1 in hepatic stellate cells in response to cytokines.


Assuntos
Colágeno Tipo I/genética , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Animais , Apoptose/efeitos dos fármacos , Sequência de Bases , Linhagem Celular , Regulação para Baixo/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Hepatócitos/citologia , Imidazóis/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Fosforilação , Piridinas/farmacologia , Ratos , Esfingomielina Fosfodiesterase/metabolismo , Regulação para Cima/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno
11.
Hypertension ; 35(6): 1197-202, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10856263

RESUMO

It has been suggested that left ventricular fibrosis in spontaneously hypertensive rats (SHR) is the result of both exaggerated collagen synthesis and insufficient collagen degradation. We have shown previously that chronic treatment with the angiotensin II type 1 receptor antagonist losartan results in diminished synthesis of collagen type I molecules and reversal of myocardial fibrosis in SHR. This study was designed to investigate whether losartan also affects the extracellular degradation of collagen type I fibers in the left ventricle of SHR. The study was performed in 30-week-old normotensive Wistar-Kyoto rats (WKY), untreated SHR, and SHR treated with orally administered losartan (20 mg/kg per day) for 14 weeks before they were killed. Ventricular collagenase activity was determined by degradation of [(14)C]collagen with tissue extracts. Ventricular expression of tissue inhibitor of metalloproteinases 1 (TIMP-1) mRNA was analyzed by Northern blot. A histomorphometric study of the left ventricle was performed in all rats. Compared with WKY, SHR exhibited left ventricular hypertrophy, increased (P<0.05) blood pressure, left ventricular collagen volume fraction and TIMP-1 mRNA, and diminished (P<0.05) collagenase activity. After the treatment period, blood pressure was higher (P<0.05) in losartan-treated SHR than in WKY, and no significant differences were noted in the remaining parameters between the 2 strains of rats. Compared with untreated SHR, treated SHR showed no left ventricular hypertrophy, diminished (P<0.05) blood pressure, left ventricular collagen volume fraction and TIMP-1 mRNA, and increased (P<0.05) collagenase activity. These results suggest that the transcription of the TIMP-1 gene is upregulated in the hypertrophied and fibrotic left ventricle of adult SHR. Upregulation of TIMP-1 may account for diminished collagenase activity in the myocardium of those rats. Chronic angiotensin II type 1 receptor blockade with losartan resulted in inhibition of TIMP-1 expression and stimulation of collagenase activity in the left ventricle of SHR. It is proposed that angiotensin II may facilitate myocardial fibrosis in SHR by depressing the collagenase-mediated extracellular degradation of collagen fibers.


Assuntos
Antagonistas de Receptores de Angiotensina , Colágeno/metabolismo , Matriz Extracelular/metabolismo , Hipertensão/metabolismo , Hipertensão/patologia , Miocárdio/patologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Colagenases/metabolismo , Fibrose , Expressão Gênica , Hipertensão/genética , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/patologia , Losartan/farmacologia , Masculino , Ratos , Ratos Endogâmicos SHR/genética , Ratos Endogâmicos SHR/fisiologia , Ratos Endogâmicos WKY , Receptor Tipo 1 de Angiotensina , Receptor Tipo 2 de Angiotensina , Fatores de Tempo , Inibidor Tecidual de Metaloproteinase-1/genética
12.
Hepatology ; 31(5): 1086-93, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10796884

RESUMO

Tumor necrosis factor alpha (TNF-alpha) is one of the key cytokines of the acute phase response and of many inflammatory processes. This cytokine has several antifibrogenic actions and down-regulates the expression of the type I collagen genes and induces the expression of metalloproteinases. Because TNF-alpha directly antagonizes some fibrogenic actions of transforming growth factor beta(1) (TGF-beta(1)), we considered it important to map the cis-acting regulatory element of the alpha1(I) collagen (col1a1) promoter involved in TNF-alpha responsiveness in hepatic stellate cells (HSC), to investigate the transcription factors that bind to it, and to establish possible mechanisms by which TNF-alpha down-regulates its expression. In this article, we show the presence of a functional TNF-alpha-responsive element (TaRE) in the -378 to -345 region of the col1a1 promoter. This element colocalizes with a previously reported TGF-beta(1)-responsive element. We further demonstrate that TNF-alpha induces nuclear translocation and binding of transcriptional complexes containing p20C/EBPbeta, p35C/EBPbeta, and C/EBPdelta to this sequence of the promoter. Transient overexpression of C/EBPdelta or p20C/EBPbeta, the natural dominant negative form of C/EBPbeta in HSC, down-regulated activity of a CAT reporter vector driven by -412 to +110 of the col1a1 promoter. Taken together, these data suggest that the -378 to -340 region of the col1a1 promoter is the site of convergence of different stimuli that ultimately modulate col1a1 gene transcription.


Assuntos
Colágeno/genética , Proteínas de Ligação a DNA/fisiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/metabolismo , Proteínas Nucleares/fisiologia , Fatores de Transcrição/fisiologia , Fator de Necrose Tumoral alfa/farmacologia , Animais , Proteínas Estimuladoras de Ligação a CCAAT , Linhagem Celular , Regulação para Baixo , Fígado/citologia , Pró-Colágeno/genética , Regiões Promotoras Genéticas , RNA Mensageiro/análise , Ratos , Elementos de Resposta
13.
Biochem Biophys Res Commun ; 259(3): 678-82, 1999 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-10364478

RESUMO

3,4-Methylenedioxymethamphetamine, MDMA ("Ecstasy"), has been previously shown to produce cell necrosis and fibrosis in the liver. Our aim was to study the effect of MDMA on the type I collagen production by a cell line of hepatic stellate cells (HSC), the cell type mainly responsible for collagen synthesis in the liver. We demonstrated that MDMA increases alpha1(I) procollagen mRNA levels and that this increase correlates with glutathione depletion and enhanced hydrogen peroxide production by HSC. Pre-treatment with either glutathione monoethyl ester or deferoxamine prevents the MDMA-induced alpha1(I) procollagen mRNA expression, indicating oxidative stress to be a mediator of this effect. Lipid peroxidation was not detected in MDMA-treated cells and therefore does not seem to be involved in the pro-fibrogenic action of MDMA on HSC.


Assuntos
Regulação da Expressão Gênica , Fígado/metabolismo , N-Metil-3,4-Metilenodioxianfetamina/farmacologia , Pró-Colágeno/metabolismo , Antioxidantes/farmacologia , Linhagem Celular , Desferroxamina/farmacologia , Relação Dose-Resposta a Droga , Glutationa/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo , Pró-Colágeno/genética , RNA Mensageiro/metabolismo , Fatores de Tempo
14.
J Hypertens ; 17(1): 107-14, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10100101

RESUMO

OBJECTIVE: Previous studies have shown that as well as left ventricular hypertrophy, myocardial fibrosis develops early in rats with spontaneous hypertension (SHR). The present study was designed to investigate whether chronic treatment with the angiotensin II type 1 (AT1) receptor antagonist losartan modifies collagen type I metabolism and reverses left ventricular fibrosis in young SHR with left ventricular hypertrophy. DESIGN: The study was performed in 30-week-old normotensive Wistar-Kyoto (WKY) rats, untreated SHR and SHR treated with losartan (20 mg/mg per day, orally) for 14 weeks before they were killed. METHODS: Ventricular pro-alpha 1 (I) collagen messenger RNA was analyzed by Northern blot. Serum levels of the carboxy-terminal propeptide of procollagen type I (PIP) and the pyridoline cross-linked telopeptide domain of collagen type I (CITP) were determined by specific radioimmunoassays as markers of collagen type I synthesis and degradation, respectively. Collagen volume fraction was determined in the left ventricle by quantitative morphometry. RESULTS: Compared with WKY rats, SHR exhibited increased (P < 0.05) mean arterial pressure, pro-alpha 1 (I) collagen messenger RNA, PIP and left ventricular collagen volume fraction, and similar CITP values. After the treatment period, mean arterial pressure was higher (P < 0.05) in losartan-treated SHR than in WKY rats. Compared with untreated SHR, treated SHR showed no left ventricular hypertrophy and diminished (P < 0.05) values of mean arterial pressure, PIP and left ventricular collagen volume fraction. No changes in pro-alpha 1 (I) collagen messenger RNA and CITP values were observed with treatment in SHR. No significant differences in the left ventricular collagen volume fraction were observed between treated SHR with normal blood pressure and treated SHR with abnormally high blood pressure at the end of the treatment period. CONCLUSIONS: These results suggest that chronic AT1 blockade with losartan decreases the post-transcriptional synthesis of fibril-forming collagen type I molecules in young SHR. This effect may be involved in the ability of this drug to reverse left ventricular fibrosis in young rats with genetic hypertension. Apart from its antihypertensive action, other mechanisms may mediate the antifibrotic effect of losartan in this animal model.


Assuntos
Anti-Hipertensivos/farmacologia , Cardiomiopatias/tratamento farmacológico , Colágeno/metabolismo , Hipertensão/tratamento farmacológico , Losartan/farmacologia , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Transcrição Gênica , Animais , Biomarcadores/sangue , Pressão Sanguínea/efeitos dos fármacos , Northern Blotting , Cardiomiopatias/metabolismo , Cardiomiopatias/patologia , Colágeno/sangue , Colágeno/genética , Colágeno Tipo I , Fibrose/tratamento farmacológico , Fibrose/metabolismo , Fibrose/patologia , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/patologia , Masculino , Peptídeos/sangue , Pró-Colágeno/sangue , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY
15.
Hepatology ; 29(3): 960-70, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10051504

RESUMO

Oxidative stress plays a key role in liver fibrosis. Both inflammatory cells and activated Kupffer cells produce H2O2, an oxidant involved in the activation of hepatic stellate cells (HSC). Increased production of reactive oxygen intermediates (ROIs) in fibrotic livers is associated in part with the up-regulation of transforming growth factor beta (TGF-beta), and this cytokine enhances collagen production by cultured HSC. However, the possible link between oxidative stress and the molecular mechanisms by which TGF-beta induces collagen gene expression in HSC remains to be elucidated. To address this question, we investigated whether H2O2 is a mediator of TGF-beta-elicited alpha1(I) collagen gene (col1a1) up-regulation. We demonstrated that TGF-beta induces the accumulation of H2O2, and that this oxidant is, in turn, directly involved in up-regulating the expression of the col1a1 gene. While the addition of H2O2 to HSC induced the expression of alpha1(I) procollagen mRNA, catalase, an H2O2 enzyme scavenger, abrogated TGF-beta-mediated col1a1 gene up-regulation. We transfected HSC with chimeric plasmids driven by different segments of the mouse col1a1 promoter and mapped a cis-acting element (-370 to -344) essential for TGF-beta responsiveness. We further showed that TGF-beta induced the activation and binding of a C/EBPbeta-containing transcriptional complex to this sequence, an effect that was also mimicked by the addition of H2O2. Taken together, these data demonstrate a direct connection between TGF-beta-mediated accumulation of H2O2 and the up-regulation of col1a1 gene in HSC.


Assuntos
Proteínas de Ligação a DNA/fisiologia , Peróxido de Hidrogênio/metabolismo , Fígado/fisiologia , Proteínas Nucleares/fisiologia , Oxidantes/metabolismo , Pró-Colágeno/genética , Fator de Crescimento Transformador beta/farmacologia , Animais , Antioxidantes/farmacologia , Proteínas Estimuladoras de Ligação a CCAAT , Catalase/farmacologia , Linhagem Celular , Núcleo Celular/metabolismo , Colágeno/genética , Genes Reporter/genética , Peróxido de Hidrogênio/farmacologia , Fígado/citologia , Fígado/metabolismo , Camundongos/genética , Oxidantes/farmacologia , Prolina/análogos & derivados , Prolina/farmacologia , Regiões Promotoras Genéticas/genética , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/metabolismo , Ratos , Elementos de Resposta/genética , Tiocarbamatos/farmacologia
16.
An Med Interna ; 14(7): 351-4, 1997 Jul.
Artigo em Espanhol | MEDLINE | ID: mdl-9410122

RESUMO

We present tuberous sclerosis affecting all the members of a family, now and for three consecutive generations (probably four). A fortuitous study of cutaneous disease in one member led to diagnosis in all of them. A systematic study detected important visceral implication in all cases, mainly neurological, despite the fact only one of then showed related symptoms. We discuss the epidemiological and diagnostic aspects of an illness, which is widely underdiagnosed even today, despite the fact that detection is by sight.


Assuntos
Esclerose Tuberosa/genética , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Tuberosa/diagnóstico
18.
Lab Invest ; 72(1): 83-91, 1995 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-7837795

RESUMO

BACKGROUND: In response to nonspecific inflammatory stimuli, circulating monocytes produce several cytokines that regulate the expression of liver acute phase protein genes. Patients with alcoholic liver disease have several manifestations of the acute phase response, including elevated serum levels of interleukin (IL)-1 (IL-1), IL-6 and tumor necrosis factor-alpha (TNF-alpha). However, the role of the acute phase response on liver fibrogenesis has not been explored. EXPERIMENTAL DESIGN: In this communication we report experiments performed to investigate whether turpentine, an acute phase response inducer in rats has any effect on alpha 1 (I) procollagen gene expression in the liver. We also investigated which of the cytokines is responsible for the turpentine effect and whether IL-6 and TNF-alpha had an effect on alpha 1 (I) procollagen mRNA expression by liver fat-storing cells (FSC). RESULTS: We show that alpha 1 (I) procollagen mRNA is increased in livers of turpentine-treated rats, and that an antibody to IL-6 as well as colchicine inhibit this effect. We also show that rIL-6 induces the expression of alpha 1 (I) procollagen mRNA in cultured FSC but not in hepatocytes. We demonstrated that the IL-6 effect is a transcriptional event that requires "de novo" protein synthesis. In addition to its effect on collagen gene expression, rIL-6 also stimulates expression of transforming growth factor-beta and fibronectin mRNAs. TNF-alpha inhibits alpha 1 (I) procollagen expression in FSC by 24 to 48 hours. However, TNF-alpha induces a transient expression of alpha 1 (I) procollagen mRNA by 2 to 3 hours. This increase is preceded by the induction of IL-6 mRNA. CONCLUSIONS: We conclude that IL-6 produced during the acute phase response, alone or in conjunction with other cytokines, could play an important role in liver fibrogenesis by inducing the expression of collagen, fibronectin, and transforming growth factor-beta mRNAs in FSC.


Assuntos
Reação de Fase Aguda/metabolismo , Interleucina-6/biossíntese , Fígado/metabolismo , Pró-Colágeno/biossíntese , RNA Mensageiro/biossíntese , Animais , Northern Blotting , Linhagem Celular , Interleucina-6/fisiologia , Metabolismo dos Lipídeos , Fígado/citologia , Ratos , Ratos Sprague-Dawley , Transcrição Gênica , Fator de Necrose Tumoral alfa/fisiologia
19.
Rev Esp Fisiol ; 50(1): 55-62, 1994 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7991941

RESUMO

The Ca(2+)-ATPase activity of the trypsin-activated CF1 presented a monophasic pattern, indicating that the active centres of the enzyme were acting with the same kinetic properties. The study of the effect of the anions cianate (OCN-) and thiocyanate (SCN-) on the ATPase activity showed the existence of cationic regulatory sites, capable of binding these modulators in a competitive way, resulting in the inhibition of the ATPase activity. Nucleotides ADP and ATP, at high concentrations, were competitive inhibitors for the substrate Ca(2+)-ATP. ATP, at low concentrations, presented an activating effect. The study of the combined effects of ATP (at low concentrations) and SCN- on ATPase activity revealed the existence of a non-competitive relationship between anions and nucleotides. The modification of CF1 with fluorescein isothiocyanate, a specific reagent that binds to amino groups of nucleotide binding centres, yielded a molar relationship FITC/CF1 = 4, both with the trypsin-treated and non treated enzyme. This specific incorporation took place on the alpha and, beta subunits of CF1, and resulted in a decrease of about 30% of the ATPase activity. These results are consistent with the existence of either three catalytic and three regulatory sites or four catalytic and two regulatory sites on CF1.


Assuntos
ATPases Transportadoras de Cálcio/química , Cloroplastos/enzimologia , Proteínas de Plantas/química , ATPases Translocadoras de Prótons/química , Difosfato de Adenosina/farmacologia , Trifosfato de Adenosina/farmacologia , Sítio Alostérico , Ânions/farmacologia , Sítios de Ligação , ATPases Transportadoras de Cálcio/metabolismo , Catálise , Ativação Enzimática/efeitos dos fármacos , Fluoresceína-5-Isotiocianato/farmacologia , Cinética , Proteínas de Plantas/metabolismo , ATPases Translocadoras de Prótons/metabolismo , Tripsina/farmacologia
20.
An Med Interna ; 11(1): 26-8, 1994 Jan.
Artigo em Espanhol | MEDLINE | ID: mdl-8025187

RESUMO

Amebiasis is a disease commonly extended all around the world, its prevalence depending on the population under study. In Spain, most cases published are of exotic acquisition. We present the case of a married couple from Venezuela presenting two different forms of invasive amebiasis: acute colitis and hepatic abscess. In our environment, once the diagnosis of amebiasis is established, a close follow-up of the patients must be made, including the evaluation of the closest contacts. Regarding the treatment, we think that the asymptomatic forms must be treated with a luminal amebicidal and the symptomatic forms, with hystic amebicidal followed by luminal amebicidal.


Assuntos
Disenteria Amebiana/diagnóstico , Abscesso Hepático Amebiano/diagnóstico , Abdome Agudo/diagnóstico , Adulto , Quimioterapia Combinada , Disenteria Amebiana/tratamento farmacológico , Disenteria Amebiana/etnologia , Feminino , Humanos , Abscesso Hepático Amebiano/tratamento farmacológico , Abscesso Hepático Amebiano/etnologia , Masculino , Metronidazol/administração & dosagem , Paromomicina/administração & dosagem , Espanha , Venezuela/etnologia
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